This invention relates to an apparatus for administering a vomiting depressant at the time of chemotherapy of cancer. More particularly, this invention relates to a percutaneous therapeutic apparatus which enables to control ooze of liquid medicine from a drug storage layer during preservation of the apparatus by laminating a pressure-sensitive adhesive for controlling ooze of medicine to a drug releasing surface, and to a percutaneous therapeutic apparatus containing serotonin-receptor antagonist which is characterized by enabling to administer the predetermined amount of the serotonin-receptor antagonist precisely and certainly to a patient.
In a field of percutaneous therapeutics, a percutaneous therapeutic apparatus such as Estraderm, Nitorderm and so forth have been conventionally developed and used clinically. However, in these conventional apparatuses, in the case of, for example, Estraderm, there occur that adhesion of the apparatus to skin decreases due to an interaction with medicine during preservation. Such decline of adhesion of a patch medicine during administration causes a decline of area for absorbing medicine and there is a case where blood concentration of drug sufficient for therapeutics can not be obtained, which may be possibly a deadly problem to the patch medicine. Several percutaneous therapeutic apparatuses have been proposed in which a medicine releasing surface and a pressure-sensitive adhesive layer having to do with adhesion to skin are separated.
For example, Unexamined Patent Publication (Kokai) No.61-265150 discloses an example in which a medicine storage layer is separated from an adhesive existing on the outer periphery of the medicine storage layer by a circumferential se. The percutaneous therapeutic apparatuses described in examples disclosed in Unexamined Utility Model Publication (Kokai) No, 60-63344, Unexamined Utility Model Publication (Kokai) No. 62-182942, Unexamined Patent Publication (Kokai) No. 62-195326, Unexamined Patent Publication (Kokai) No1-224312, Examined Patent Publication (Kokoku) No. 4-46592, Japanese National Publication No. 6-503252, Unexamined Patent Publication (Kokai) No.-1283 and Unexamined Patent Publication (Kokai) No. 62-212320 are common to Unexamined Patent Publication (Kokai) No. 61-265150 on the point that an interaction of the pressure-sensitive adhesive layer on the periphery of the medicine releasing surface with the medicine storage layer are disconnected.
However, when such pressure sensitive adhesive layers as described in these examples are placed to the periphery of the medicine-releasing surface, the apparatus as a whole is bulky and, as a result, adhesion to skin lowers. There is a fear of increase in skin irritation in cases where the area of the pressure sensitive adhesive is enlarged in order to rise the adhesion or adhesive force.
On the other hand while serotonin (5-HT3)-receptor antagonist which is used as antiemetic for inhibiting vomiting which occurs often at the time of administration of cancer chemotherapeutic is used in therapeutics by oral administration and so forth, the control of blood concentration of drug is difficult and there occurs a problem that side effect on extrapyramidal motor system. In recent years, developments of a patch medicine have been tried in order to solve these problems as proposed in, for example, Examined Patent Publication (Kokoku) No. 5-79646 and so forth which, however, encounter a problem of adhesion to skin and which hardly exhibit sufficient drug efficacy. And, a patch medicine in which butyrophenone-group drug is contained in acrylic ester polymer base is proposed in Unexamined Patent Publication (Kokai) No. 8-113533. However, an acrylic type pressure-sensitive adhesive is low in its drug releasing property and has a strong irritation to skin, and, it is no, therefore, equal to long-term continuous administration. And, there is fear that these pharmaceutical preparations the release of which is not controlled rise blood concentration temporarily because of rapid rising of initial release and increase an occurrence of side effect.
The problems to be solved by this invention are to get rid of lowering of adhesion resulted from an interaction of an apparatus with medicine during preservation of the apparatus and increase of skin irritation accompanying with enlargement of bulk caused by placing a pressure-sensitive adhesive layer on the periphery.
And, this invention relates to an apparatus for supplying to skin surface an effective amount of serotonin-receptor antagonist for therapeutics from a liquid medicine storage layer through a medicine releasing layer and, more particularly, relates to a percutaneous therapeutic apparatus the medicine-releasing surface of which is sealed to make a loss in medicine substantially zero when using the apparatus and which is able to apply to a patient the predetermined amount of the serotonin-receptor antagonist precisely and certainly.
Inventors of this invention have made devotedly many researches and developments in order to solve the aforementioned problems. As a result, we have discovered that release of drug can be controlled and simultaneously medicine can be prevented from oozing by making use of a medicine-releasing layer comprising a pressure-sensitive adhesive layer which is able to control the release of drug in a percutaneous therapeutic apparatus. That is to say, according to the percutaneous therapeutic apparatus of this invention having a medicine-releasing layer comprising a pressure-sensitive adhesive layer which is able to control release of the drug, good adhesion can be obtained and increase of skin irritation resulted from enlarged bulk can be prevented and, simultaneously, ooze of the medicine can be prevented during preservation and an effective amount of the medicine for therapeutics can be released precisely and certainly from the present apparatus after sticking the present apparatus on skin of a patient.
That is to say, this invention provides a percutaneous therapeutic apparatus which enables;
(1) to control release of medicine by a simple structure,
(2) to improve preservation-stability of medicine,
(3) to lower irritation to skin,
(4) to obtain good adhesion to skin,
(5) to obtain high cohesive force of a pressmen sensitive adhesive.
This invention relates to a percutaneous therapeutic apparatus having at least three layers comprising;
(A) a medicine non-permeable backing layer,
(B) a medicine storage layer containing serotonin-receptor antagonist between the backing layer and a medicine-releasing layer,
(C) a pressure-sensitive layer which is able to control release of medicine.
The percutaneous therapeutic apparatus of this invention can be provided with a release liner layer which is able to be released when using outside the aforementioned medicine-releasing layer. And, the medicine-releasing layer of this invention which controls the release of medicine can include a medicine-permeable film (hereinafter, sometimes referred to as porous layer) other than for the pressure-sensitive adhesive layer.
Further, the invention also provides a percutaneous-absorption pharmaceutical preparation containing serotonin-receptor antagonist which can be administered stably over a long period of times.
More in detail, this invention provides a percutaneous therapeutic apparatus having a medicine-releasing layer containing a pressure-sensitive adhesive layer enabling to control release of drug comprising pressure-sensitive adhesive containing rubber elastomer, tackifier resin and softening agent or pressure-sensitive adhesive further containing acrylic type pressure-sensitive adhesive other than these components.
Further more in detail, the pressure-sensitive adhesive layer of this invention is prepared by applying the aforementioned pressure-sensitive adhesive to whole area of the medicine-releasing surface.